Aplasia cutis congenita in surviving co-twin after propylthiouracil exposure in utero

Aplasia cutis congenita (ACC) has been observed after fetal exposure to the antithyroid drug methimazole (MMI), but not reported after propylthiouracil (PTU), the current antithyroid drug of choice during pregnancy. This occurrence has implications for patient information and causal research

Genome-wide gene expression profiling of the Angelman syndrome mice with Ube3a mutation

Angelman syndrome (AS) is a human neurological disorder caused by lack of maternal UBE3A expression in the brain. UBE3A is known to function as both an ubiquitin-protein ligase (E3) and a coactivator for steroid receptors. Many ubiquitin targets, as well as interacting partners, of UBE3A have been identified. However, the pathogenesis of AS, and how deficiency of maternal UBE3A can upset cellular homeostasis, remains vague. In this study, we performed a genome-wide microarray analysis on the maternal Ube3a-deficient (Ube3am−/p+) AS mouse to search for genes affected in the absence of Ube3a. We observed 64 differentially expressed transcripts (7 upregulated and 57 downregulated) showing more than 1.5-fold differences in expression (P<0.05). Pathway analysis shows that these genes are implicated in three major networks associated with cell signaling, nervous system development and cell death. Using quantitative reverse-transcription PCR, we validated the differential expression of genes (Fgf7, Glra1, Mc1r, Nr4a2, Slc5a7 and Epha6) that show functional relevance to AS phenotype. We also show that the protein level of melanocortin 1 receptor (Mc1r) and nuclear receptor subfamily 4, group A, member 2 (Nr4a2) in the AS mice cerebellum is decreased relative to that of the wild-type mice. Consistent with this finding, expression of small-interfering RNA that targets Ube3a in P19 cells caused downregulation of Mc1r and Nr4a2, whereas overexpression of Ube3a results in the upregulation of Mc1r and Nr4a2. These observation help in providing insights into the genesis of neurodevelopmental phenotype of AS and highlight specific area for future research

Winnicott, Donald

Winnicott was a British psychoanalyst famous for identifying an area of experiencing between inner psychic life and social reality called the potential space. In his work, potentiality is what can emerge on the basis of what is already there, or, in other words, it is there, where new possibilities can emerge. The idea of potentiality – and a practical concern with the possibility of possibility – can be found at the heart of all aspects of his work. First, as a researcher, he pragmatically expanded the psychoanalytical tradition on the basis of his unique clinical experience. Second, as a theoretician, he developed an understanding of human development whereby the child emerges as a person within a good-enough environment, and, in a first phase, differentiates from the carer thanks to a complex and paradoxical process of self-formation through symbol use. These observations led him to propose the ideas of transitional phenomena or potential space. What might be called “potential phenomena” (or phenomena of potentialization) mark the beginning of symbolism in the play between infant and carer and evolve via more elaborate child’s play into the cultural experiencing and creativity that can continue throughout adulthood. Third, in his clinical work, Winnicott considered psychotherapy as a technique for creating a potential space to engage in a form of shared play. For children or adults who lacked the possibility to play, these therapeutic spaces aimed to provide a good enough environment –institutional, relational – within which the person can come to experience phenomena of potentialization which render the possible, possible